gemcitabine plus albumin-bound paclitaxel in patients with advanced metastatic pancreatic cancer

Conditions: Metastatic Pancreatic Cancer

Summary: to determine the maximum tolerated dose and dose-limiting toxicity of gemcitabine plus albumin-bound paclitaxel (abi-007) in patients with advanced metastatic pancreatic cancer.

albumin-bound paclitaxel is a novel, solvent-free, albumin-bound, 130 nanometer particle form of paclitaxel designed to avoid the problems associated with solvents used in taxol(abraxane prescribing information 2005). albumin has a number of properties that make it an attractive molecule to combine with paclitaxel. albumin is a natural transporter of endogenous hydrophobic molecules such as water-insoluble vitamins and hormones (vorum 1999)and albumin binding to the gp-60 receptor (albondin) initiates the caveolae-mediated endothelial transport of protein-bound and unbound plasma constituents (john et al 2003, minshall et al 2003, tiruppathi et al 1997). this study consisted of a phase 1 dose escalation phase, a phase 2 treatment phase and a 24-month follow-up phase.

Eligibility criteria:
inclusion criteria: * patient has histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. patients with islet cell neoplasms are excluded. * male or non-pregnant and non-lactating female, and age greater or equal to 18. * if a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test beta-human chorionic gonadotropin (b-hcg) documented within 72 hours of the first administration of study drug. * if sexually active, the patient must agree to use contraception considered adequate and appropriate by the investigator. * patient must have received no prior therapy for the treatment of metastatic disease. prior treatment with 5-fluorouracil (5-fu) or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. if a patient received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least 6 months after completing the last dose of gemcitabine. * patient has the following blood counts at baseline * absolute neutrophil count (anc) equal or greater to 1.5 x 10\^9/l; * platelets equal or greater to 100 x 10\^9/l * hemoglobin equal or greater to 9 g/dl. * patient has the following blood chemistry levels at baseline: * aspartate aminotransferase (sgot), alanine aminotransferase (sgpt) equal or less than 2.5 x upper limit of normal range (uln) is allowed * bilirubin less than or equal to uln * serum creatinine within normal limits or calculated clearance equal or greater to 60 ml/min/1.73m\^2 patients with serum creatinine levels above the institutional normal value * patient has no clinically significant abnormalities in urinalysis results * patient has acceptable coagulation status as indicated by a prothrombin time (pt) within normal limits (plus or minus 15%) and partial thromboplastin time (ptt) within normal limits (plus or minus 15%). * patient has a karnofsky performance status (kps) greater or equal to 70 (eastern cooperative oncology group \[ecog\] ps 0-1). * patient has one or more metastatic tumors measurable by computed tomography (ct) scan. * patient has been informed about the nature of study, and has agreed to participate in the study, and signed the informed consent form prior to participation in any study-related activities. exclusion criteria: * patient has known brain metastases unless previously treated and well controlled for at least 3 months (defined as stable clinically, no edema, no steroids and stable in two scans at least 4 weeks apart). * patient uses therapeutic coumadin for a history of pulmonary emboli and deep vein thrombosis (dvt). * patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy. * patient has known infection with human immunodeficiency virus (hiv), hepatitis b, hepatitis c. * patient has undergone major surgery, other than diagnostic surgery i.e.-- done to obtain a biopsy for diagnosis without removal of an organ), with 4 weeks prior to day 1 of treatment in this study. * patient received radiotherapy, surgery, chemotherapy, or an investigational therapy within 3 weeks prior to study entry weeks (6 weeks for nitrosureas or mitomycin c). * patient has a history of allergy or hypersensitivity to the study drug. * patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug. * patient is unwilling or unable to comply with study procedures. * patient is enrolled in any other clinical protocol or investigational trial.

Keywords: metastatic pancreatic cancer, abraxane, gemcitabine